IN SITU RANTES AND INTERFERON-γ GENES EXPRESSION IN PEDIATRIC SMALL BOWEL CROHN'S DISEASE

Abstract

Aims: Rantes (regulated upon activation, normal T cell expressed and secreted) is a chemotactic cytokine for memory T lymphocytes, monocytes and eosinophils. Interferon-γ (IFN-γ) is a key cytokine responsible for immune response. To visualize their distribution and to understand their possible role in the selective accumulation of inflammatory cells in Crohn's disease (CD), we analysed the expression of Rantes and IFN-γ genes from patients with CD using in situ hybridization (ISH) on frozen and paraffin tissue sections. Méthods: We studied intestinal and mesenteric lymph node samples from 9 children who had undergone ileal resection for CD. The samples were examined for the presence of epithelioid-giant cell granulomas (EGCG). Normal pediatric intestine (n=5) and lymph nodes (n=2) served as controls. Radiolabelled Rantes and IFN-γ mRNA probes were used. Results: Positive signal with the Rantes antisense probe was present within numerous cells in all CD specimens in the epithelial compartment, lamina propria and within EGCG. Labelled cells were identified in paraffin sections as lymphocytes, macrophages, and epithelioid cells. Only scattered Rantes positive cells were present in the intestinal control tissues. Numerous Rantes positive cells were observed in control lymph nodes exhibiting follicular hyperplasia. IFN-γ positive cells were present in all CD specimens in ileal and lymph node specimens, predominantly in close contact with EGCC. No positive signal was obtained with Rantes and IFN-γ sense probes. Conclusions: These findings suggest Rantes and IFN-γ participation in the selective accumulation of macrophages and memory T helper lymphocytes inside granulomas and in the inflammatory infiltrate both of which are characteristics of CD.